Citation

Saurat JH, Kaya G, Saxer-Sekulic N, Pardo B, Becker M, Fontao L, Mottu F, Carraux P, Pham X, Barde C, Fontao F, Zennegg M, Schmid P, Schaad O, Descombes P, Sorg O. Toxicol. Sci. 2012; 125(1): 310-317.

Affiliation

Swiss Centre for Applied Human Toxicology, University of Geneva, Switzerland.

Copyright

(Copyright © 2012, Oxford University Press)

DOI

10.1093/toxsci/kfr223

PMID

21998131

Abstract

Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne", are the most specific sign of abnormal dioxin exposure, and classically used as a key marker in humans. We followed for five years a man who had been exposed to the most toxic dioxin, TCDD, at a single oral dose of 5 million-fold more than the accepted daily exposure in general population. We adopted a molecular medicine approach, aimed at identifying appropriate therapy. Skin lesions, which progressively covered up to 40% of the body surface were found to be hamartomas which developed in parallel to a complete and sustained involution of sebaceous glands, with concurrent transcriptomic alterations pointing to the inhibition of lipid metabolism and the involvement of bone morphogenetic proteins signalling. Hamartomas created a new compartment that concentrated TCDD up to 10-fold compared to serum, and strongly expressed the TCDD metabolizing enzyme CYP1A1, thus representing a potentially significant source of enzymatic activity, which may add to the xenobiotic metabolism potential of the classical organs such as the liver. This historical case provides a unique set of data on the human tissue response to dioxin for the identification of new markers of exposure in human populations. The herein discovered adaptive cutaneous response to TCDD also points to the potential role of the skin in the metabolism of food xenobiotics.

Language: en